Combined immunosuppressive treatment (CIST) in lupus nephritis: a multicenter, randomized controlled study

Clin Rheumatol. 2019 Apr;38(4):1047-1054. doi: 10.1007/s10067-018-4368-8. Epub 2018 Nov 28.

Abstract

Objectives: The standard strategy for treating lupus nephritis comprises glucocorticoids together with either intravenous cyclophosphamide or oral mycophenolate mofetil, but the low remission rate is still a challenge in practice. This study was aimed to seek higher remission rate of lupus nephritis using a combined strategy.

Method: A 24-week trial was conducted in 17 rheumatology or nephrology centers in China. A total of 191 lupus nephritis patients were randomized to follow a combined immunosuppressive treatment (CIST) with intravenous cyclophosphamide, an oral immunosuppressive agent, namely mycophenolate mofetil, azathioprine or leflunomide, and hydroxychloroquine (n = 95), or receive intravenous cyclophosphamide alone (n = 96) for 24 weeks. Glucocorticoid was given to both groups. The primary end point was a complete remission with a most stringent standard as proteinuria < 150 mg per 24 h, normal urinary sediment, serum albumin, and renal function at 24 weeks. The secondary end point was treatment failure at 24 weeks.

Results: At week 24, both the rate of complete remission (39.5%) and total response (87.2%) was higher in the combined group, compared with CYC group (20.8% and 68.8%, p < 0.05). The cumulative probability of complete remission was also higher in the combined group (p = 0.013). In addition, the combined treatment was superior to routine CYC with less treatment failure (12.8% vs.31.2%, p < 0.001). No difference was found between the incidences of severe adverse events in the two arms: 3.2% (3/95 combined group) vs.4.2% (4/96 CYC group).

Conclusion: Treatment with a combined immunosuppressive agent is superior to routine CYC only therapy in lupus nephritis.

Keywords: Immunosuppressive agents; Lupus nephritis; Remission inducing; Systemic lupus erythematosus.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Azathioprine / therapeutic use*
  • Cyclophosphamide / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Leflunomide / therapeutic use*
  • Lupus Nephritis / drug therapy*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use*
  • Remission Induction
  • Treatment Outcome
  • Young Adult

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Leflunomide
  • Mycophenolic Acid
  • Azathioprine